A study published in Annals of Internal Medicine on July 14, 2026, found that veterans with type 2 diabetes who added a GLP-1 receptor agonist to basal insulin therapy did not discontinue insulin at higher rates compared to those who added other glucose-lowering agents. Over three years, 16.7% of…
A research team led by Dr. Kasia J. Lipska from the Yale School of Medicine in New Haven, Connecticut, conducted a target trial emulation to compare the effects of adding various glucose-lowering agents to basal insulin therapy in veterans with type 2 diabetes. The study analyzed data from patients who began treatment between 2020 and 2022 with either a glucagon-like peptide-1 receptor agonist GLP-1 RA , a sodium-glucose cotransporter 2 inhibitor SGLT2i , or a dipeptidyl peptidase-4 inhibitor DPP-4i . The research included 8,869 matched sets of patients across the three medication groups, ensuring balanced comparisons. The goal was to determine whether GLP-1 RAs, which are known for their cardiovascular and weight benefits, also help patients discontinue insulin more effectively than other oral agents.
The study was published online July 14 in the peer-reviewed Annals of Internal Medicine. It underwent editorial and scientific review processes that included fact-checking and proofreading to ensure credibility. The researchers specifically focused on veterans already receiving basal insulin for type 2 diabetes, a population that often faces challenges in simplifying complex medication regimens.
In the intention-to-treat analysis over three years of follow-up, 16.7% of patients who initiated a GLP-1 RA discontinued basal insulin therapy. For those starting an SGLT2i, the discontinuation rate was 17.9%, and for those on a DPP-4i, it was 17.1%. The risk ratios for insulin discontinuation when comparing GLP-1 RAs to SGLT2is was 0.93 with a 95% confidence interval of 0.86 to 1.01. When compared to DPP-4is, the risk ratio was 0.98 with a 95% confidence interval of 0.87 to 1.09. These results indicate that the differences between the groups are not statistically significant, meaning that GLP-1 RAs do not provide a meaningful advantage in facilitating insulin cessation.
A modified per-protocol analysis, which accounted for adherence and protocol deviations, did not show substantively different results. Additionally, no subgroup of patients, whether defined by baseline characteristics or comorbidities, demonstrated a comparative advantage for GLP-1 RAs over the other agents in terms of insulin discontinuation. The consistency across all analyses reinforces the conclusion that GLP-1 RAs, when added to basal insulin, do not specifically drive higher rates of insulin discontinuation.
The authors of the study noted, "Although GLP-1 RAs remain valuable for their cardiovascular, renal and weight benefits, their initiation alone does not seem to drive basal insulin discontinuation beyond that observed with other glucose-lowering agents." This quote highlights the balance between the known benefits of GLP-1 RAs and the findings of this particular study. The research does not diminish the importance of GLP-1 RAs for other health outcomes but clarifies their role in the context of insulin de-escalation.
Peptides referenced: Glucagon, GLP-1.
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